title: Weak hydrogen bonds formed by thiol groups in N-acetyl-(L)-cysteine and their response to the crystal structure distortion on increasing pressure.
abstract: The effect of hydrostatic pressure on single crystals of N-acetyl-l-cysteine was followed at multiple pressure points from 10(-4) to 6.2 GPa with a pressure step of 0.2-0.3 GPa by Raman spectroscopy and X-ray diffraction. Since in the crystals of N-acetyl-l-cysteine the thiol group is involved in intermolecular hydrogen bonds not as a donor only (bonds S-H···O) but also as an acceptor (bonds N-H···S), increasing the pressure does not result in phase transitions. This makes a contrast with the polymorphs of l- and dl-cysteine, in which multiple phase transitions are observed already at relatively low hydrostatic pressures and are related to the changes in the conformation of the thiol side chains only weakly bound to the neighboring molecules in the structure and thus easily switching over the weak S-H···O and S-H···S hydrogen bonds. No phase transitions occur in N-acetyl-l-cysteine with increasing pressure, and changes in cell parameters and volume vs pressure do not reveal any peculiar features. Nevertheless, a more detailed analysis of the changes in intermolecular distances, in particular, of the geometric parameters of the hydrogen bonds based on X-ray single crystal diffraction analysis, complemented by an equally detailed study of the positions of all the significant bands in Raman spectra, allowed us to study the fine details of subtle changes in the hydrogen bond network. Thus, as pressure increases, a continuous shift of the hydrogen atom of the thiol group from one acceptor (a carboxyl group) to another acceptor (a carbonyl group) is observed. Precise single-crystal X-ray diffraction and polarized Raman spectroscopy structural data reveal the formation of a bifurcated S-H···O hydrogen bond with increasing pressure starting with ∼1.5 GPa. The analysis of the vibrational bands in Raman spectra has shown that different donor and acceptor groups start "feeling" the formation of the bifurcated S-H···O hydrogen bond in different pressure ranges. The results are discussed in relation to some of the previously published data on the effect of high pressure on the polymorphs of l-cysteine, dl-cysteine, and glutathione, that show similarity with the effects reported here for N-acetyl-l-cysteine. The results obtained in this work allow one to suggest new models for the pressure-induced structural rearrangements in the whole family of cysteine-containing crystals.
authors.affiliation: Novosibirsk State University , 2 Pirogov str., 630090 Novosibirsk, Russian Federation.
authors.forename: Vasily S
authors.initials: VS
authors.lastname: Minkov
authors.forename: Elena V
authors.initials: EV
authors.lastname: Boldyreva
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D006874:Hydrostatic Pressure; D008968:Molecular Conformation; D013059:Spectrum Analysis, Raman; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013696:Temperature
chemical_list: D013438:Sulfhydryl Compounds; D006859:Hydrogen; D000111:Acetylcysteine